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Biomedical subjects

S Kaneda

Publications and source records attributed to S Kaneda.

At least 55 records · Page 3Linked to original sources

Regulatory sequences clustered at the 5' end of the first intron of the human thymidylate synthase gene function in cooperation with the promoter region.

A human thymidylate synthase (TS) minigene containing 5'- and 3'-flanking sequences, all the exons, and only intron 1 showed a normal frequency of stable transformation when transfected into TS-negative mutant cells, whereas minigenes in which intron 1 was replaced by intron 2 or deleted in the above construct showed only a few percent of the above frequency. Introduction of intron 1 into the above intronless or intron 2 minigene restored the transforming activities regardless of its position and orientation. Deletion analysis revealed two positive and one negative regulatory sequences in the 5' end of intron 1, each of which seemed to bind specific proteins as shown by gel shift analysis. Intron 1 also stimulated expression of a TS promoter-CAT gene construct but not that of an SV40 promoter-CAT gene construct. These results indicate that the multiple regulatory sequences clustered in intron 1 stimulate TS gene expression in concert with the 5'-flanking sequences.

Gene Expression Regulation, Enzymologic↗

Complementation by a cloned human ubiquitin-activating enzyme E1 of the S-phase-arrested mouse FM3A cell mutant with thermolabile E1.

A temperature-sensitive growth mutant tsFS20 isolated from mouse FM3A cells was identified as a mutant with thermolabile ubiquitin-activating enzyme E1 by transfection with a full-length cDNA encoding the human E1 enzyme and cell-cell hybridization with an authentic E1 mutant ts85 previously isolated from FM3A cells. The resulting transformants produced thermoresistant E1 activity. Upon shift-up of temperature, asynchronously growing tsFS20 cells showed multiple points of cell-cycle arrest. At the nonpermissive temperature, tsFS20 cells that had been synchronized at the G1-S-phase progressed and accumulated in the mid-S-phase, as evidenced by the absence of G2-specific cdc2 kinase activity, while ts85 mutant cells, the widely used E1 mutant, reached the G2-phase and were arrested. Thus, the E1 mutation seemed to be involved in progression in the S-phase as well as in the G2-phase in the cell cycle. Degradation of short-lived abnormal proteins in tsFS20 cells was decreased to about 50% at the nonpermissive temperature, while the block was fully restored to the wild-type level in the transformant cells. Relevance of the unusually high incidence of the temperature-sensitive E1 mutation was discussed in terms of the E1 as a determinant of heat tolerance of cells.

Animals↗

Disseminated intravascular coagulation in lupus erythematosus with acute liver damage.

A case of disseminated intravascular coagulation (DIC) in a patient with systemic lupus erythematosus (SLE) with acute liver dysfunction is described. A 37-year-old man with SLE developed acute DIC and marked liver damage after fracture of the right clavicle and pharyngitis. Treatment with high-dose steroids, heparin, antithrombin III, gabexate mesilate, and antibiotics resulted in prompt improvement. The recovery of an SLE patient after acute DIC and marked liver damage is considered very rare. We report here such a case and discuss the previous reports.

Adult↗

[Studies on metoclopramide (MCP) loading test during pregnancy and puerperium for the evaluation of lactating capacity].

To evaluate the correlation between prolactin (PRL) secreting capacity and puerperal lactation, 66 women who had delivered normally without any complications during pregnancy were studied. They were divided into two groups depending on the lactating state a month after the delivery: The breast feeding group (group A, 40 cases), and the supplementary feeding group (group B, 26 cases), respectively. 10 mg of metoclopramide (MCP) loading was carried out in the 36th week of gestation and in the third day of the puerperium, and serum levels of PRL (at 0, 30, 60 min. after the MCP loading) were measured by RIA. Serum levels of insulin, glucose, triglyceride, free fatty acid, cholesterol and lipoproteins were also examined. There was no significant change in the serum levels of the various, substances during pregnancy and puerperium. Also, no significant change could be seen in the MCP loading test in the 36th week of gestation. However, on the third day of puerperium, serum PRL after 30 min. of the MCP loading showed a significant increase in group B compared with group A (587.1 +/- 202.9 vs. 431.2 +/- 196.6 ng/ml, p less than 0.02, mean +/- standard deviation). These results suggested that the MCP loading test during the early stage of puerperium might be an important index to use in determining whether the mother was ready to breast feed.

Female↗

Structural and functional analysis of the human thymidylate synthase gene.

The complete nucleotide sequence of the human thymidylate synthase (TS) gene was determined. The biologically active unit spans about 16 kilobase pairs (kbp) and is composed of seven exons and six introns. The promoter region and the major transcriptional start sites were located within about 400 base pairs (bp) and 160-180 bp, respectively, upstream from the ATG initiation codon. A minigene consisting of a 5'-flanking sequence of about 4 kbp, a coding sequence of about 1.7 kpb was sufficient for cell cycle-dependent expression of TS when introduced into a TS-deficient mutant of rodent cells. The 5'-flanking region does not contain a "TATA," "CAAT," or the consensus sequence for Sp1 binding (GC box), whereas intron 1 contains three GC boxes. The gene is G + C-rich and the CpG-rich region extends from 5'-flanking region to intron 1. These sequence characteristics were compared with those of the mouse TS gene and other cell cycle-regulated genes.

Animals↗

[Liver abscess as a complication of TAE--risk factors and prevention].

Transcatheter hepatic arterial embolization for not only hepatocellular carcinoma but metastatic liver cancers is nowadays prevalent. Gall bladder infarction, cholangitis, peptic ulcers, pancreatitis, and aneurysm are reported as complications of it. But the liver abscess following it is rare. We reviewed three cases of liver abscesses after transcatheter hepatic arterial embolization. Biliary tract congestion and inflammation, and iatrogenic contaminations are supposed to major factors that caused liver abscesses. We think we should refrain from the embolization until biliary tract disorders are resolved and take care not to contaminate the proceeding materials in addition to mixing antibiotics with embolus.

Biliary Tract Diseases↗

[Comprehensive approach to clinical background and effect of bromocriptine administration in patients with endocrinological polycystic ovarian disease].

Present study was performed to elucidate the clinical features and the treatment of so-called endocrinological polycystic ovarian disease (PCO). 36 cases out of 189 infertile patients who had various ovulatory disturbances were subjected during past four years. They were selected by the definitions as follows; 1) serum LH levels greater than or equal to 30 mIU/ml and serum FSH levels less than or equal to 15 mIU/ml, 2) hyper-response of LH secretion by LH-RH (100 micrograms) loading test; maximum values greater than or equal to 250 mIU/ml. Serum androstenedione (ASD), dehydroepiandrosterone-sulfate (DHA-S), estrone (E1), estradiol (E2), progesterone (P, in the mid-luteal phase) and testosterone (T) levels were examined by RIA method for the purpose of the evaluation of the endocrinological background of the PCO in Japanese women. The same examinations were also done in 8 volunteer women who had normal ovulatory menstrual cycles for the control study. In 6 cases of the PCO patients who showed biphasic BBT charts, the endometrial biopsy was done in the mid-luteal phase at the same time of the blood sampling. And the correlation between various serum hormone levels and the endometrial morphology in the PCO patients was also discussed. Then bromocriptine (5 mg/day) was administered in these patients for more than 30 days and the effect of the treatment was investigated. Serum ASD levels in the PCO patients were significantly higher than those in the control (2.52 +/- 1.30 vs. 1.43 +/- 1.21 ng/ml, M +/- S.D., p less than 0.05), while serum E2 and P levels in the patients were significantly lower than those in the control (E2: 118.6 +/- 39.5 vs. 192.5 +/- 53.9 pg/ml, p less than 0.005. P: 7.26 +/- 5.08 vs. 124.4 +/- 4.6 ng/ml, p less than 0.005, respectively). There were no significant differences in serum levels of the other hormones. By the administration of bromocriptine, serum ASD levels decreased (1.62 +/- 1.34 ng/ml, p less than 0.05), and E2 (177.9 +/- 48.6 pg/ml, p less than 0.025) and P (11.8 +/- 4.3 ng/ml, p less than 0.005) levels increased significantly into the levels of control. Serum LH levels of the patients were also suppressed by the treatment of bromocriptine (42.5 +/- 13.7 vs. 27.4 +/- 12.0 mIU/ml, p less than 0.005), however there was no change in serum FSH levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Two cases of solid and cystic tumor of the pancreas (including one case of MRI)].

Solid and cystic tumor of pancreas is an uncommon neoplasm which is histologically low grade malignant but amenable to cure by surgical excision. It tends to occur in young women. US and CT depict a well circumscribed mass that can be solid, mixed solid and cystic and largely cystic. Their ratio depends on the degree of hemorrhage and necrosis. Angiography shows a mildly to moderately vascular mass which corresponds to solid parts. MRI is useful to detect the hemorrhage which is common in this tumor.

Adolescent↗

Regional assignment of the human thymidylate synthase (TS) gene to chromosome band 18p11.32 by nonisotopic in situ hybridization.

The human thymidylate synthase (TS) gene was regionally assigned to chromosome band 18p11.32 by nonisotopic in situ hybridization using biotinylated cDNA (1.1 kb insert) and genomic DNA (6.8 kb insert) probes of the human gene. There have been two provisional assignments for the TS gene to 18pter-q12 and 18q21-qter. The present result confirmed the first of these and further localized the TS gene to the telomeric region of the short arm of chromosome 18. The TS gene appears to be a novel telomeric anchor point for the construction of both physical and genetic linkage maps of human chromosome 18.

Chromosomes, Human, Pair 8↗

Identification and characterization of an L1 family sequence with a very long open reading frame in the third intron of the human thymidylate synthase gene.

A long L1 repetitive sequence (3.6 kilobase pairs) was found in the third intron of the human thymidylate synthase gene. This L1 family sequence is unique in that it possesses the longest open reading frame (1.7 kilobase pairs) of all L1 family members identified in sequences associated with specific genes that have been cloned thus far. Furthermore, the amino acid sequence deduced from the open reading frame of the L1 sequence was found to be highly homologous (90%) to that encoded by a known human teratocarcinoma L1 RNA species, and to contain several blocks of sequences homologous to ones in RNA-dependent DNA polymerases of various origins.

Amino Acid Sequence↗

Human thymidylate synthase gene: isolation of phage clones which cover a functionally active gene and structural analysis of the region upstream from the translation initiation codon.

Two genomic DNA fragments partially encoding human thymidylate synthase (TS) [EC 2.1.1.45] were previously cloned in lambda phage from the mouse cell transformant, but had no transforming activity on mouse TS-negative mutant cells. In this study, an additional genomic DNA for human TS was cloned and demonstrated to have the transforming activity in combination with one of the two previously cloned DNAs and to produce human TS mRNA. The two transforming genomic DNAs overlapped and covered a region of 23 kb in total. Using fragments from one of these DNAs, the structure of the 1.2-kb region around the ATG initiator codon of the TS gene was analyzed in relation to regulatory sequences of the gene. Sequence determination demonstrated the presence of an unusual inverted repeat consisting of a triple tandem repeat of a 28-bp sequence and an inverted sequence of the same length. These sequences can form three possible, stable, stem-loop structures, which may be interconvertible. Based on S1 nuclease mapping data and a line of circumstantial evidence, we deduced two major mRNA cap sites within the inverted sequence. Comparison of the human and mouse sequences upstream from the ATG initiator codon revealed many significant blocks of sequence homology, especially in the regions around the deduced cap sites.

Animals↗

The effects of class IA antiarrhythmic drug on the common type of atrial flutter in combination with pacing therapy.

In 11 patients with common type of atrial flutter (common AF), rapid atrial pacing from the high right atrium was performed before and/or after class Ia antiarrhythmic drug administration, confirming transient entrainment by decreasing the pacing cycle length by 10 ms. In 10 patients before the drug administration, common AF was not interrupted although the pacing cycle length was decreased to 200 ms in 5 patients, accelerated atrial flutter or atrial fibrillation was induced in 4 patients, and common AF was converted into sinus rhythm in only 1 patient. After the drug administration common AF was converted into sinus rhythm in 5 out of 6 patients. The class Ia antiarrhythmic drug prolonged the common AF cycle length (255 +/- 12 ms vs. 298 +/- 37 ms, p less than 0.005) and widened the entrainment zone (64 +/- 7 ms vs. 90 +/- 20 ms, p less than 0.05). The widening of the entrainment zone and the prolongation of the common AF cycle length facilitate the successful conversion of common AF at a longer pacing cycle length, which would not precipitate atrial fibrillation or accelerated atrial flutter. The combination therapy of rapid atrial pacing and the class Ia antiarrhythmic drug is thought to be useful in the therapy of common AF.

Adult↗

Treatment of atrial flutter and rapid atrial tachycardia with transesophageal atrial pacing.

Eight patients with atrial flutter (AF) and rapid atrial tachycardia (AT) (5 common AF, 1 uncommon AF and 2 AT) were treated with transesophageal atrial pacing (TEAP). In 5 patients no antiarrhythmic agent was used during this study, and in 3 patients procainamide was administrated intravenously. Conversion to sinus rhythm was successfully achieved in 7 patients (5 common AF and 2 AT). Two patients were converted to sinus rhythm immediately after pacing, and transient atrial fibrillation was induced before conversion to sinus rhythm in 5 patients. TEAP failed to terminate the arrhythmia in 1 patient with uncommon AF. Administration of procainamide reduced the atrial rate in 2 common AF and 1 AT, which were successfully converted to sinus rhythm by TEAP, but induced a rapid ventricular response in 2 patients, one of whom also developed hypotension before conversion. No significant complication due to TEAP was observed in this study. In conclusion, TEAP is a noninvasive method with fewer complications and has nearly the same high efficacy for converting AF and rapid AT to sinus rhythm as DC cardioversion or transvenous atrial pacing.

Aged↗

[Diagnosis and treatment of impotence with administration of chemical prosthesis using real-time mechanical sector duplex scanner--with special reference to diabetic patients].

The usefulness of a chemical prosthesis was studied for the diagnosis and treatment of 20 patients with erectile impotence (14 due to diabetes, 2 due to pelvic surgery and 4 due to psychogenic factors) using papaverine hydrochloride and phentolamine mesilate. Absolute erection was observed in 16 patients (80%) and coital penetration was possible in all 9 patients who actually tried sexual intercourse. Penile arterial blood flow was measured in 15 patients using a real-time mechanical sector duplex scanner (Diasonics DRF/400V) just before and after the chemical prosthesis, and a marked increase in blood flow was observed in all patients after administration. From these results, it is considered that measurement of the penile blood flow using a mechanical sector duplex scanner is useful in the diagnosis and monitoring of impotence. Furthermore, a chemical prosthesis is suitable mainly for the treatment of impotence due to diabetes, by adjusting the dosage and administration.

Adult↗

[Intended super-ovulation with HMG in the treatment of so-called functional sterility].

To investigate a new treatment for so-called functional sterility, 17 out of 456 infertile patients were treated in the past three years (age: 32.7 +/- 3.6 years old, infertile period: 5.9 +/- 1.4 years, M +/- S.D.). These patients were treated with HMG-HCG. The injection of HMG (75-450iu) was started on the 5th day of the menstrual cycle, and the follicular development was observed by ultrasonography. Then, HCG (10,000-20,000iu) was injected when 3 or 4 matured follicles (with a diameter greater than 20mm) were observed. In some cases, the endometrial biopsy was done in the mid-luteal phase and the effect of the treatment was examined morphologically. Pregnancies were observed in 6 cases (35.3%) and all of them were singletons. One of them spontaneously aborted at 9 weeks of gestation, but remaining five cases delivered at full term without any complications. The total dose of HMG was 2,116.8 +/- 843.3iu, and OHSS was observed in 5 cycles out of 31 cycles (16.1%). There was no other severe complication during the treatment. The growth of the endometrium thickened in the treated cases, but no time lag in endometrial dating could be found in the morphological study. These results indicated that the intended superovulation method for the treatment of so-called functional sterility was effective through the mechanism of the improvement of the implantation ratio.

Adult↗

Clinical study of late potentials--comparison of late potentials in myocardial infarction, cardiomyopathy and idiopathic ventricular tachycardia.

Late potentials (LPs) were studied using the signal averaging technique in 80 patients with myocardial infarction (MI), idiopathic cardiomyopathy (CM) and idiopathic ventricular tachycardia (IVT). In MI, LP duration was 28.4 +/- 12.6 ms in the sustained VT group (I; 8 cases); 18.6 +/- 9.0 ms in the non-sustained VT group (II; 11 cases); and 14.4 +/- 8.6 ms in the non-VT group (III; 21 cases); (p less than 0.05 in I vs II, p less than 0.01 in I vs III and not significant in II vs III). In CM, it was 33.7 +/- 13.0 ms in group I (6 cases); 20.1 +/- 5.9 ms in group II (12 cases); and 7.1 +/- 9.2 ms in group III (14 cases); (p less than 0.01 in I vs II, I vs III and II vs III). The LP duration in IVT (8 cases) was 15.6 +/- 10.4 ms, which was significantly shorter than that of group I in MI and CM (p less than 0.05 vs MI and p less than 0.01 vs CM). Late potential duration was also compared between a pacing-inducible VT group and a non-inducible VT group. The mean value of LP duration in the inducible VT group of MI was significantly longer than that in the non-inducible group (27.8 +/- 3.9 ms in 4 cases vs 17.3 +/- 2.5 ms in 4 cases, p less than 0.05). However, there was no significant difference in LP duration between the inducible and non-inducible groups of CM (22.0 +/- 11.0 ms in 5 cases vs 22.2 +/- 13.6 ms in 5 cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Effects of obesity and weight gain during pregnancy on obstetrical factors].

The relationship between the body weight or weight gain during pregnancy and various obstetrical factors was investigated in 731 patients who delivered in San-ikukai Hospital for in the year 1986. The patients were classified into three groups according to their body weight in non-pregnant states: slender (n = 214), ordinary (n = 379) and obese (n = 138), according to the standard for "The decision diagram for the estimation of obesity and emaciation in Japanese" published in 1986 by the Ministry of Health and Welfare, Japan. Each of these groups was further divided into two groups according to the degree of weight gain during pregnancy (more or less than 15kg). Then, the duration of labor, the blood loss during delivery, the birth weight, the placental weight and the obstetrical abnormalities (prolonged labor, arrested labor, blood loss of more than 500 ml, fetal distress and toxemia of pregnancy) were investigated in these groups. The blood loss, the neonatal birth weight and the placental weight in the obese groups were much greater than those in the ordinary or the slender group (p less than 0.005). However, there was no significant difference in the duration of the labor among these groups. The incidence of obstetrical abnormalities in the obese group was significantly higher than in the ordinary or the slender group (chi 2 = 4.37, p less than 0.05, chi 2 = 5.27, p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗